Adaptation of plasminogen activator sequences to known protease structures

FEBS Letters

Ötting, F.²  Straßburger, W.³  Pitts, J.E.¹  Steffens, G.J.²  Tickle, I.J.¹  Glover, I.D.¹  Wollmer, A.³  Blundell, T.L.¹  Flohé, L.²  Günzler, W.A.² 

[1] Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, England;Grünenthal GmbH, Forschungszentrum Aachen-Eilendorf, Abteilung Proteinchemie, Zieglerstr. 66, D-5100 Aachen, FRG;Lehr- und Forschungsgebiet Struktur und Funktion der Proteine, Abteilung Physiologische Chemie, RWTH Aachen, Forckenbeckstraße, D-5100 Aachen, FRG

关键词: Urokinase;    Tissue-type plasminogen activator;    Chymotrypsin;    Trypsin;    Model building;    Computer graphics;    Sequence alignment;    β-Structure formation;    UK;    urokinase;    HUK;    high molecular mass urokinase;    LUK;    low molecular mass urokinase;    TPA;    tissue plasminogen activating enzyme;    CT;    chymotrypsin;    T;    trypsin;    PTI;    pancreatic trypsin inhibitor;    E;    elastase;    SCR;    structurally conserved region;   

DOI  :  10.1016/0014-5793(83)80551-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The sequences of urokinase (UK) and tissue-type plasminogen activator (TPA) were aligned with those of chymotrypsin, trypsin, and elastase according to their ‘structurally conserved regions’. In spite of its trypsin-like specificity UK was model-built on the basis of the chymotrypsin structure because of a corresponding disulfide pattern. The extra disulfide bond falls to cysteines 50 and 111d. Insertions can easily be accommodated at the surface. As they occur similarly in both, UK and TPA, a role in plasminogen recognition may be possible. Of the functional positions known to be involved in substrate or inhibitor binding, Asp 97, Lys 143 and Arg 217 (Leu in TPA) may contribute to plasminogen activating specificity. PTI binding may in part be impaired by structural differences at the edge of the binding pocket.

【 授权许可】

Unknown